Fig 1.
The figure depicts the schematic of the methodology applied in this study.
Fig 2.
Switch genes with an unfavourable prognostic value from the survival analysis on TCGA data.
Kaplan-Meier analyzes to evaluate the correlations between the expression of the basal-like specific switch genes and the OS in TCGA breast invasive carcinoma patients. Low- and high-expression groups refer to patients with expression levels lower and greater than the 50th percentile, respectively.
Table 1.
Summary of the properties of the basal-like prognostic biomarkers.
Fig 3.
Expression of the switch genes with an unfavourable prognostic value across the PAM50 breast cancer subtypes.
Gene expression levels of the 11 basal-like specific switch genes point out from the Kaplan-Meier survival analysis in TCGA breast invasive carcinoma patients affected by the four BC subtypes of PAM50 classification. The black dashed line reported in each plot indicates the median value used in the Kaplan-Meier survival analysis to split the low-expression and high-expression group. One-way ANOVA test was used to compare the means of the selected genes among the patients’ groups. T-test was used to perform multiple pairwise-comparisons and statistical significance was indicated by the star symbols (i.e., ns: p > 0.05, *: p ≤ 0.05, **: p ≤ 0.01, ***: p ≤ 0.001, ****: p ≤ 0.0001).
Fig 4.
Linear regression model fitting.
The median expression of the basal-like prognostic biomarkers is plotted against the phenotype varying from physiological to pathological condition (a) and against the pathological staging (b). Solid lines represent how the linear model fits the data. We showed, as a representative example, the results corresponding to the highest values of the model fitting index R-squared: R-squared (rounded to one decimal place) ≥ 0.9 for the subtype (a) and ≥ 0.7 for the staging (b).
Fig 5.
Immunohistochemistry results from the Human Protein Atlas.
Representative immunohistochemistry images of the indicated switch genes in BC tissues and normal breast tissues obtained from the Human Protein Atlas.
Fig 6.
Gene regulatory network of the basal-like prognostic biomarkers.
a) Network of the regulatory interactions among the identified switch genes and the known transcription factors (TFs). Light blue nodes represent switch genes; grey nodes represent transcription factors. b) TFs with a statistically significant prognostic value according to the Kaplan-Meier survival analysis. Kaplan-Meier analyzes to evaluate the correlations between the expression of the TFs and the OS in TCGA breast invasive carcinoma patients. Low- and high-expression groups refer to patients with expression levels lower and greater than the 50th percentile, respectively. c) Expression of the TFs in the gene regulatory network across the PAM50 breast cancer subtypes. The black dashed line reported in each plot indicates the median value used in the Kaplan-Meier survival analysis to split the low-expression and high-expression group. One-way ANOVA test was used to compare the means of the selected genes among the patients’ groups. T-test was used to perform multiple pairwise-comparisons and statistical significance was indicated by the star symbols (i.e., ns: p > 0.05, *: p ≤ 0.05, **: p ≤ 0.01, ***: p ≤ 0.001, ****: p ≤ 0.0001).
Fig 7.
Genomic and epigenomic alterations of the basal-like prognostic biomarkers.
a) Heatmap with dendrogram representing the unsupervised hierarchical clustering analysis based on CNVs data of TCGA-BRCA patients. The rows in the heatmap represent the 11 basal-like prognostic biomarkers. The columns correspond to basal-like and luminal A TCGA-BRCA patients: basal-like are indicated in dark blue and luminal A in green. The cells of the heatmap represent the log2 segment mean value of CNVs (ranging from -1 up to 3.5), for which colour code is indicated in the scale on the right-hand side of the figure. b) Heatmap with dendrogram representing the unsupervised hierarchical clustering analysis based on DNA methylation data of TCGA-BRCA patients. The rows in the heatmap represent the 11 basal-like prognostic biomarkers. The columns correspond to basal-like and luminal A TCGA-BRCA patients: basal-like are indicated in dark blue and luminal A in green. The cells of the heatmap represent beta-value (ranging from 0 to 1) extracted from Illumina 450k normalized data, for which colour code is indicated in the scale on the right-hand side of the figure. c) Distribution plot of beta-value of CENPN, GSDMC, PRAME and CTPS genes in basal-like and luminal A patients. Dashed lines represent the mean of beta-values for each patients’ group.